A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis

Abstract

Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1–4 hours on day 1 and 450–600 mg over 1–3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts ( N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1–2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( p = 0.003) and a 10.6% decrease in T2 lesion volume ( p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients

“…The goal of this study was to monitor the lymphocyte profile in patients on ublituximab therapy to further our understanding about mechanism of action of B cell depletion therapy in MS. Ublituximab efficiently depleted peripheral B cells in the patients in this study and the patients had an improved clinical outcome (Fox et al, 2018). Within 24 h of the first dose of ublituximab, the percentage of B cells declined from a mean of 7.3% to 0.2%, and this level of B cell depletion was maintained for the 24 week study period.…”

“…The goal of this study was to determine if monitoring lymphocyte subsets following B cell depletion with ublituximab could shed light on the possible mechanism of action of B cell depletion in MS. Importantly, the patients in this study had a significant clinical improvement with reduction in lesion burden and relapse rate (Fox et al, 2018).…”

“…Patients received a second dose of ublituximab at week 3. No significant recovery of B cells during the 24 week monitoring period was seen, illustrating that ublituximab rapidly and efficiently depletes peripheral blood B cells in MS patients (Fox et al, 2018).…”

B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic — when immunosuppression meets infection?

“…Ublituximab is a novel chimeric glycoengineered IgG1 that binds a unique epitope on CD20 and demonstrates increased binding capacity to CD20. Ublituximab was recently tested in a phase-II, 48-week, placebo-controlled study, which was designed to assess its optimal dose and infusion time in 48 patients with relapsing forms of MS [44]. [46].…”

Monoclonal Antibody Therapies for Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

“…A phase-2 study of relapsing MS enrolled 48 patients, and ublituximab was infused on days 1 and 15 and during week 24. 89 The optimal dose was determined by comparing the efficacy of B-lymphocyte depletion and the safety and tolerability (450 or 600 mg over an infusion time of 1-4 hours). The median amount of B-lymphocyte depletion was more than 99% at week 4 (the primary analysis point), and this was maintained at weeks 24 and 48, with no significant differences between the cohorts.…”